Quantum Tunneling on Carbene Organocatalysis: Breslow Intermediate Formation via Water-Bridges

The Breslow intermediate is key to several NHC-organocatalyzed reactions. However, accessing the Breslow intermediate via a direct intramolecular hydrogen atom transfer (HAT) is unlikely and can only occur if it is aided, for instance, by a water molecule. Herein we show computationally that for a model thiazolium-based NHC catalyst quantum mechanical tunneling (QMT) significantly accelerates the water-bridged HAT in the Breslow intermediate formation. Although the reaction can proceed through a semiclassical mechanism, the contribution of thermally activated tunneling is dominant (3–82 times faster on the studied systems). Considering that traces of water are known to catalyze intramolecular HAT in many reactions, these results may allude to a general role of QMT in these processes.